Tetradecafluorohexane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

November 2019

Reliability:

other: Not relevant for an expert statement

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2018

Report date:

2019

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

This theoretical assessment was prepared, taking all currently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance.

GLP compliance:

no

Remarks:

Not applicable

Test material

Test material information

Constituent 1

Reference substance name:

Tetradecafluorohexane

EC Number:

206-585-0

EC Name:

Tetradecafluorohexane

Cas Number:

355-42-0

Molecular formula:

C6F14

IUPAC Name:

tetradecafluorohexane

Test material form:

liquid

Applicant's summary and conclusion

Conclusions:

5. TOXICOKINETIC ASSESSMENT

A substance can enter the body via de gastrointestinal tract, the lungs, and the skin1. Since different parameters are relevant for absorption via the different routes of exposure, the uptake via these three routes will be addressed individually.
After oral administration, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract.1 Since the water solubility of Tetradecafluorohexane is very low (≤0.1 mg/L), the substance is expected to be poorly dissolved in gastrointestinal fluids,
therefore the availability for uptake is limited. Based on its moderate molecular weight (338), uptake via passive diffusion might occur, but might be too big for passage through aqueous pores or carriage across membranes with the bulk passage of water, also because its water solubility is low. Tetradecafluorohexane has a relatively high partition coefficient (log Pow ≥ 4.5), which is considered not favourable for passive diffusion, but the uptake via micellular solubilisation by bile salts can be expected to take place, enhancing the absorption. The substance does not have ionisable groups that could than can influence its absorption. For risk assessment purposes, oral absorption of Tetradecafluorohexane is set at 10%, based on its low water solubility, moderate molecular weight and high log Pow. The oral toxicity data do not provide reasons to deviate from the proposed oral absorption factor.2
Tetradecafluorohexane has low water solubility, so its dissolution in mucus lining in the respiratory tract may be limited. Moreover, Tetradecafluorohexane has a high partition coefficient (log Pow ≥ 4.5), which is considered not favourable for passive diffusion through biological membranes. However, Tetradecafluorohexane has a high vapour pressure (30.9 kPa at 20°C), which indicates that Tetradecafluorohexane is highly volatile (vapour pressure
>25 kPa) and exposure by inhalation is possible. Very lipophilic vapours (log Pow >4) have the ability to reach the deep lung, where absorption through gas exchange may occur.2 Tetradecafluorohexane is a liquid, which indicates that exposure via areosols is also possible. Aerosols can reach the tracheobronquial region of the respiratory tract. Taking in consideration all these factors together, it is concluded that for risk assessment purposes, as a worst case scenario, the inhalation absorption should be set at 100%.2
Tetradecafluorohexane is a liquid with very low water solubility, it will only dissolve to a very small extent into the surface moisture of the skin to allow uptake. The relatively high log Pow (>4) indicates the crossing of epidermal barriers will be limited. According to the criteria given in the REACH Guidance2, a default value of 100% dermal absorption has been established if the molecular weight is lower than 500 and log P between -1 and 4. The physical/chemical properties of Tetradecafluorohexane do not fully meet the criteria for full dermal absorption (MW 338; log Pow ≥4.5). As it is generally accepted that dermal absorption is not higher than oral absorption, for risk assessment purposes a dermal absorption of 10% will be considered as a more realistic worst case2. Tetradecafluorohexane is neither skin irritating nor corrosive, so enhanced uptake related to local effects need not to be considered.

Once absorbed, distribution of the substance throughout the body is expected to be limited based on its very low water solubility, relatively high log Pow and moderate molecular weight. Orally absorbed Tetradecafluorohexane may be metabolized in the gastrointestinal tract or the liver and excreted through bile and urine. As a very volatile substance, it may be excreted through exhaled air.3 Based on its relatively high partition coefficient (log Pow ≥ 4.5), Tetradecafluorohexane may accumulate in adipose tissue (intracellular concentration may be higher than the extracellular concentration). However, based on its very low water

solubility and high molecular weight, the overall bioaccumulation potential of Tetradecafluorohexane is expected to be low.

6. CONCLUSION
A toxicokinetic assessment was performed based on the available data of the substance. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 10% (oral), 100% (inhalation) and 10% (dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.

Executive summary:

A toxicokinetic assessment was performed based on the available data of the substance. Based on the physical/chemical properties of the substance, absorption factors for this substance are derived to be 10% (oral), 100% (inhalation) and 10% (dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.